Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Approximately 1 in 50 individuals carry a genetic mutation within the survival motor neuron (SMN) gene that increases the likelihood of a child being born with spinal muscular atrophy (SMA). Mutations within this gene render cells incapable of producing SMN protein vital for the survival and development of motor neurons involved in muscle control. Insufficient levels of SMN results in the degradation of the neuronal network accompanied by the breakdown and death of muscle tissue. This muscle-wasting disease has no cure and a poor prognosis, resulting in increased morbidity and mortality. With the prevalence of the disease occurring in 1 in 10,000 births and the majority of treatments solely focused on palliative care, more research is necessary to develop both a more accurate prognostic tool as well as a cure. Our laboratory recently discovered that in healthy individuals, SMN is released by cells and stored inside of exosomes. Exosomes are small vesicles used in cell-to-cell communication to transport molecules such as RNA and protein. Therefore, our research will attempt to: 1) examine the potential for SMN levels within exosomes to predict the disease outcome, to use as a prognostic tool, and, 2) utilize the exosome communication technique by constructing exosomes loaded with SMN protein and deliver them to SMN deficient cells. Further work will utilize cell culture and animal models to evaluate the efficiency and efficacy of SMN loaded exosomes in correcting the SMA phenotype in cells and animals lacking SMN. By quantifying the natural levels of SMN found within exosomes derived from patient serum, exosomes may offer a new, more accurate tool for SMA prognosis. Additionally, by administering SMN through a process that mimics healthy cell communication, our research may offer a new, effective means for treatment of SMA, potentially slowing its progression, reversing its destruction and increasing the likelihood of survival.